Human Growth Hormone
Term for - syndrome that results when the anterior pituitary gland produces excess GH after epiphyseal plate closure at puberty. A number of disorders may increase the pituitary's GH output, although most commonly it involves a tumor called pituitary adenoma, derived from the somatotrophs.
Acromegaly
DA is produced where?
Arcuate nucleus
GHRH is produced where?
Arcuate nucleus
What improves genetic predicatibility of human growth?
Being well nourished
Why can IGF-1 injection cause hypoglycemia?
Cause high dose can cross react with insulin receptors in muscle
Whats Laron Syndrome
GH receptor disorder - high GHRH, low IGF-1, high GH - short stature
What is insulin's involvement in growth
Growth factor especially in utero and in children
What is IGF-2's involvement in growth
Growth promoting hormone during gestation. "Major fetal growth factor"
Whats the difference between hypothyroid dwarfs and non-hypothyroid dwarfs
Hypothyroid - maintain infantile proportions non-hypothyroid - develop adult proportions just in a smaller size
GH reuglates post-natal growth mostly via ________
IGF-1
Pigmies are unable to produce what?
IGF-1
What stimulates proliferation and differentiation of chondrocytes (bone growth)
IGF-1
What stimulates proliferation and differentiation of myoblasts to grow muscle
IGF-1
Which hormone is critical for intrauterine growth
IGF-1
IGF-1 is structurally similar and can cross react with what molecules
IGF-2 and inuslin
Term for - autosomal recessive disorder characterized by an insensitivity to growth hormone (GH), caused by a variant of the growth hormone receptor. It causes short stature and a resistance to diabetes and cancer
Laron's Syndrome
Term for - a rare lethal familial condition marked by slow physical and mental development, wide-set eyes, low-set ears, hirsutism, and severe endocrine disorders, such as enlargement of the clitoris and breasts in females and of the phallus in males.
Leprechaunism or Donohue's Syndrome
What is made in adipocytes taht acts on the arcuate nucleus to give sensation of satiety
Leptin
Failure to treat a hypothyoroid state in a child will result in what? What if you treat it later?
Mental retardation and slow growth Growth will catch up but mental effects are permanent
GHRH stimulates what cells to secrete GH
Somatotrophs
Whats another name for growth hormone
Somatotropin
Describe regulation of GH
Stimulated by: GHRH Ghrelin DA opposing SST Inhibited by: SST IGF-1 GH itself feeds back to inhibit GHRH and stimulate SST
What is true regarding use of GH as performance enhancing drug
Strong evidence shows GH has no effect on muscle mass or strength. Some evidence that combined with testosterone it has some affect
What effects do GC's have on growth rate
They slow development of chondrocytes - so growth will slow, but there will be catch up growth after removal of the GC's
Satiety center is located where? What about hunger center?
Ventromedial nucleus Lateral hypothalamic area
What is the role of androgens and estrogens in growth
Very important in pubertal growth spurt -- too much leads to faster growth but smaller window and shorter stature
What is thyroid hormones involvement in growth
important for in utero and early childhood development
Bone growth occurs where? By what cells?
Epiphyseal Plates Chondrocytes
GH activates receptors to use what pathway
JAK/STAT
IGF-1 half life is what
15-20 mins
Whats the dominant form of GH
22kDa form
What causes females growth to plateau earlier than males
Estrogen closing epiphyseal plates
Term for - a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones
Cretinism
What can cause fetal macrosomy?
Diabetic mother with high insulin leading to high birth weight
What are the 2 distinct effects of GH
Direct - increasing metabolism of proteins, lipids, and glycogen Indirect - promoting growth effects through stimulating IGF-1 production by liver and most tissues
SST is produced where?
Dorsomedia lnucleus
What are the major hormonal determinants of linear growth in normal post-uterine life
GH and IGF-1
Describe GH effects on muscle glucose uptake, lipolysis, and gluconeogenesis
Increases gluconeogenesis decreases uptake increases lipolysis makes tissues insulin resistant
What are the locations of IGF-1 feedback?
Inhibits somatotrophs Inhibits GHRH release in arcuate nucleus Increases SST release from dorsomedial nucleus
Most of pulsatile GH release is when? What can increase GH release?
Night time Exercise, stress, high protein meal, fasting
Is human growth linear?
No - it is episodic, w/ major growth events as an infant and in puberty
Does IGF-1 handle all growth effects?
No GH has some effects that are not well known
Whats the most important extrinsic factor affecting growth
nutrition
How much of human heigh is genetic and how much is nutrition
probably 60-80% genetic 20-40% nutrition
Children with diabetes have faster or slower growth rates
slower - insulin is a growth factor
IGF-1 acts through what signaling pathway
tyrosine kinase receptor